Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system

Baumann, Gert; Sb, Felix; Schrader, Jürgen; Cd, Heidecke; Rieß, Gotthard; Wd, Erhardt; Ludwig, Liesel; U, Loher; Sebening, F; Blömer, H

doi:10.1007/bf01852128

Cited by 33 publications

(7 citation statements)

References 25 publications

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“…The absolute values of AC activity clbtained in this study are also considerably higher, expressed in picomoles CAMP formed per mg protein per minute, than found in our previous study, and in other studies on human myocardial material [14,20,211. The cause of this may partly be imprecise protein estimation in very diluted homogenates.…”

Section: Discussioncontrasting

confidence: 47%

Catecholamine-responsive adenylate cyclase activity in human endomyocardial biopsies

Golf

Jahnsen

Simonsen

et al. 1985

Scandinavian Journal of Clinical and Laboratory Investigation

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In the present study we have examined adenylate cyclase (AC) activity, the stimulation by isoproterenol and inhibition by propranolol, in endomyocardial biopsies from eleven patients with suspected cardiomyopathy. Biopsies were obtained by heart catheterization from the right endomyocardial surface of the interventricular septum. Three biopsies were taken from each patient (mean weight, 2.1 mg; range, 1.2-4.0 mg). One biopsy was studied by light microscopy. The two other biopsies were homogenized and AC activity in the homogenates was determined in the presence of different concentrations of isoproterenol and isoproterenol (5 micrograms/ml) combined with different concentrations of propranolol. Thus stimulation and inhibition curves were established for a pair of biopsies from each patient. Appropriate biopsy material was obtained in triplicate from only seven patients. In these patients the variance in maximal receptor stimulation (by isoproterenol) and inhibition (by propranolol) was significantly smaller in pairs of biopsies compared to the variance between all biopsies (p values from less than 0.05 to less than 0.025). Hence it is possible to determine AC activity, and adrenergic receptor function, in very small endomyocardial biopsies. New diagnostic possibilities could thereby be introduced.

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Section: Discussioncontrasting

confidence: 47%

Catecholamine-responsive adenylate cyclase activity in human endomyocardial biopsies

Golf

Jahnsen

Simonsen

et al. 1985

Scandinavian Journal of Clinical and Laboratory Investigation

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“…However, since in recent reports [3,15] cardiac H2-receptors and cardiac ill-receptors were characterized in both, human and guinea pig myocardium with practically identical receptor properties in both species, speculation is provided that results of the present study may be of clinical relevance for patients with acute and chronic heart failure. Our results demonstrate, that long-term treatment with flsympathomimetic drugs, e.g.…”

Section: Discussionmentioning

confidence: 80%

Apparent superiority of H2-receptor stimulation and simultaneousβ-blockade over conventional treatment withβ-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium

et al. 1984

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Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to beta-adrenergic and H2-histaminergic stimulation by isoproterenol and impromidine tested in the isolated perfused heart preparation. Adenylate cyclase activity as well as binding characteristics of [3H]-dihydroalprenolol ([3H]-DHA), [3H]-methyl-tiotidine ([3H]-TIOT) and [3H]-quinuclidinyl benzilate ([3H]-QNB) to cardiac beta 1-, H2- and cholinergic muscarinic receptors were determined in sarcolemmal membrane preparations of the right ventricle of the same hearts. In addition, an attempt was made to elucidate the therapeutic value of post-AMI treatment with impromidine in the presence and absence of beta-blockade, in contrast to administration of prenalterol and the conventional therapy with beta-sympathomimetic drugs, e.g. dobutamine. Three days post-AMI the dose-response curve for isoproterenol of right ventricular dP/dtmax was significantly depressed, while the inotropic effect of impromidine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 80% whereas impromidine and NaF stimulation rates were unaltered. Receptor-binding studies indicated a 90% loss and 10-times lowered affinity (KD) of the remaining beta-receptors while specific [3H]-TIOT- and [3H]-QNB-binding was unchanged. Administration of dobutamine increased mortality rates and extension of infarct size, led to a further decrease in contractile response to isoproterenol, induced complete insensitivity of adenylate cyclase to isoproterenol stimulation and caused pronounced additional reduction of number and affinity of [3H]-DHA-binding sites. In contrast, all above alterations were prevented by treatment with either prenalterol or combined administration of impromidine plus metoprolol. It is concluded, that these alterations in the non-ischemic, uninvolved myocardium post-AMI are the result of catecholamine-induced specific damage of sarcolemmal beta-receptors. Furthermore, treatment with H2-agonists in combination with beta-blocking agents may have beneficial effects, whereas conventional therapy with beta-sympathomimetic drugs tends to worsen the already depressed function of the beta-adrenergic stimulation mechanism.

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“…The histamine-mediated cardiac events are characterized by the dualism of two different receptors. Via He-receptors, histamine mediates positive inotropic and chronotropic effects [6,9,16,27,35]. The occurrence of tachyarrhythmias was also found to be H2-receptor-mediated [26].…”

Section: Discussionmentioning

confidence: 99%

Systemic anaphylaxis—separation of cardiac reactions from respiratory and peripheral vascular events

1990

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An anaphylactic reaction in the isolated perfused heart is characterized by a drastic coronary constriction, arrhythmias, and an impairment of contractility. In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to ascertain the electrocardiographic and cardiovascular changes during systemic hypersensitivity reactions. In addition, an attempt was made to differentiate cardiac from respiratory events. In guinea pigs, sensitization was produced by s.c. administration of ovalbumin together with Freund's adjuvant solution. Fourteen days after sensitization, the effects of an i.v. infusion of ovalbumin were tested in the anesthetized guinea pigs, which were ventilated with room air or 100% oxygen. A second administration of the antigen induced the development of cardiovascular collapse, leading to death within 12 min. Within 3 min, cardiac output decreased by 90% and end-diastolic left ventricular pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in the form of atrioventricular block. Left ventricular contractility declined continuously within the first 4 min. Finally, after 4 min, blood pressure steadily decreased. During ventilation with room air, severe hypoxia developed, with arterial PO2 decreasing from 94 mmHg to 14 mmHg after 3 min. However, under ventilation with 100% oxygen, a dissociation between cardiac damage and respiratory distress occurred. Myocardial ischemia and signs of cardiac failure preceded the development of hypoxia by a significant time interval. It is to be concluded that cardiac damage is a primary event in anaphylactic shock. Furthermore, the electrocardiographic signs of ischemia are interpreted as a result of coronary artery spasm.

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Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system

Cited by 33 publications

References 25 publications

Catecholamine-responsive adenylate cyclase activity in human endomyocardial biopsies

Catecholamine-responsive adenylate cyclase activity in human endomyocardial biopsies

Apparent superiority of H2-receptor stimulation and simultaneousβ-blockade over conventional treatment withβ-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium

Systemic anaphylaxis—separation of cardiac reactions from respiratory and peripheral vascular events

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